1. Precocious Puberty case reviews
Nadia Muhi Iddin
Endocrinology PLEAT
Conquest hospital 8/7/2011

2. Case 1 Term baby. Born locally. 2.8Kg
Primigaravida 18 year old mother.
Uneventful pregnancy and delivery.
No significant medical history.
Family now had a 4 month old baby at time of child referral to paediatric services.

3. 3/2008
GP referral at 3.5 year with 2 month history of breast development and rapid growth.
Seen with in a month. Had single episode of vaginal bleeding & abdominal pain.
No headache or visual symptoms.
Past history of mild eczema.
Breast stage B3 bilateral. No pubic or axillary hair growth. Family thought is was ( puppy fat)
Height & weight 98th centile (2002 growth chart)
Child now had 2 younger siblings 2 year old sister and 7 month old brother.

4. Investigations TFT,FSH, LH, 17B oestardiol.
Urgent MRI Head/Pituitary with gadolinium under GA.
Urine steroid profile.
FBC, LFT, Ca Profile, U&E, creatinine, Bicarbonate, Iron levels.
Bone age ( left hand & wrist)
Pelvic and renal US.

5. Blood test results. Date LH FSH 10/03/08 5.1 7.9 02/06/08 0.4 1.2
08/09/09
1.6
4.2
18/01/10
2.4
3.3
15/03/10
3.7
6.3

6. Bone age report Date Chronological age Bone age 10/3/2008 3y 6 months
8.9 years
02/02/2010
5y 5 months
9.1 years

8. management
Diagnosis of Gonadotropin dependant central precocious puberty.
Discussion with paediatric endocrinologist & parents and maternal grandfather.
Discussion with pharmacy for medication.
Managements included Cryptoterone acetate 50mg tablet.
IM injections at hospital. Gonapeptyl depot 3.75mg ( Triptorelin) 6/5/2008.
Further vaginal bleed.
4 weeks interval. Commenced on Decapeptyl SR 11.25mg Tritorelin IM injection on 12 week interval.
Local appointment with paediatric endocrinologist 1/7/2008.
Offer of referral to CAHMS.
Home care nursing team for the injections.

9. Follow up
1/2009. Injection interval reduced to 11 weeks. Becomes moody before injections.
Illness 9/2009 reduced energy .
Mother coping with appointments and 3 young children.
Started reception year and school support at home. ( play therapy)
7/2009 reduced to 9 weeks interval. LH.FSH not completely suppressed.
2/2010 reduced to 8 week interval. Mother & child happy.

10. Continued
4/2010 family disruption and lost appointment. Moved with grandparents
3/2010 product change needles.
2/2010 repeat bone age.
Follow up 6 monthly and annual with endocrinologist.
No concerns started ballet. Went on holiday.

11. Case 2 Term female baby Born at the Conquest.
3425 gm birth weight. 11/2005
Admitted at 5 weeks for RSV Bronchiolitis.
Admitted at 10 weeks with croup.
Admitted at 11 moths swallowed a dishwasher calgon tablet.
Presented at 2years 5months because of rapid Growth in the last year. HV referral.

12. History Always big baby with length near 91 centile.
Parents tall mid parental height 91st centile-98th.
Currently in 5-6 year old cloths.
Older brother of 7 years and a shorter 5 year old brother.
Current height and weight above 99.8th centile.
Grown 4.8cm in 4 months.
HV referral.

13. Examination Pubic hair stage 2 Breast stage 3 Body odour
White vaginal discharge.
No headaches, visual symptoms, faints or fits.

14. Investigations FBC,LFT,U&E, Creatinine. Bicarbonate.
Ca profile and protein
TFT,LH,FSH,IGF1,oestardiol. Prolactine
Tumour markers AFP, Serum B HCG
Bone age
MRI head under GA
Pelvic & renal US.

15. Management At age 2 years and 9 months. 8/2008
Treptoreline ( Gonapeptyl) IM injection.
Oral Crypriterone acetate.
Followed in 4 weeks .
Meetings with family and printed information. Contact with nurse team.
Blood stained discharge 9/2008.

16. Bone age Date Chronological age Bone age 2/6/2008 2 y 6 months 7.3 y
12/08/2010
4y 9 months
7.4 y

17. Hormonal tests Date 17.beta oestradiol LH FSH 12/08/08 184pmol/l 3.5
8.9
05/11/09 97
3.0
1.6
14/10/10
<73
0.6
0.9

18. Other investigations Presenting IGF1:47.3 (4-20)
Presenting IGFBP3: 3.4 ( )
Prolactin:1842mU/L. Repeat test 190mU/L
Urine steroid profile qualitatively normal.
Pelvic US was difficult but reported both ovaries mature with follicles. Left 22mmX15mmUterus mature.

19. Progress 10/2008 Blood stained vaginal discharge.
Mother concern about appetite.
3/2009 Reduced injections to every 10 weeks.
11/2009 Mood changes 1 week before medication.
1/2010 technical difficulties revert to 4 weekly medication. Stress.
1/2011 Unwell for 3 weeks unrelated illness.
6 monthly and annual follow up. Growth and endocrine.

21. Precocious Puberty
True precocity refers to an abnormally early puberty in which physical changes follow a normal progression and lead to full sexual maturity.
Age below 8 years in girls and 9 in boys.
Variant under age 6 in girls and under 8 for menarche.
Partial forms of precocious puberty.

22. Cause of precocious puberty

23. Incomplete/ false/LHRH independent/ pseudo puberty

24. Incomplete continued

25. Incomplete/LHRL in both sexes
McCune-Albright syndrome
Primary hypothyroidism. Long standing
Exogenous sex steroid exposure.
Partial forms of Precocious Puberty
Premature thelarche
Premature adrenarche
Premature isolated menarche.
The 1st 2 are much more common.

26. McCune –Albright syndrome
Irregular skin pigmentation
Fibrous bone dysplasia
Endocrine autonomy of glands notably ovaries.
Very enlarged ovaries with solitary cysts
Precocious puberty with early vaginal bleeding.
*Gene map locus 20q13.2
Bone fractures
Ref: Geneva foundation for
medical education& research.

27. Premature thelarche Infant or young girl Transient/ Cyclical
Often asymmetrical
No growth acceleration or other pubertal features.
Parallel follicular development but uterus remains small.
Self limiting but may progress to early puberty.

28. Premature adrenache /Pubarche
Normal mid childhood 6-8 years increase in adrenal androgens due to maturation of Zona reticularis.
Modest growth spurt.
Early pubic hair
Advanced bone age.
More common in girls
If before age 6 or increasing exclude CAH and adrenal tumours.

29. Guide to examination Detailed examination in girls under 6 years
Abnormal sequence or virilisation in girls.
Neurological symptoms, hypertension or abnormal growth.
Testicular palpation in boys.

30. Issues to consider Explanation. 90% Ideopathic in girls.
Support. Child. Family and school
Suppressing medications. GnRh analogues
Monitoring of growth. Rate and puberty.
Bone age.
Monitoring of hormonal levels.
Final height.
Side effects of medication.

31. Treatment requires specialist management
Gonadotropin depend precocious puberty :Gonadorelin analogues
Aim:
Delay development of secondary sex characteristics
Reduce growth velocity
Gonadotropin Independent precocious puberty.
Crypterone is a progesterone with anti-androgen activity used in gonodotropine independent Precocious Puberty/
Testolactone
Spironolactone.

32. Gonadorelin analogues
Goserelin. Not licensed for use in children.
Implant 2 manufacturers.
Leuprorelin acetate.Not licensed for use in children. 1 manufacturer. ( 4 & 12 week)
Subcutaneous or IM injection.
Triptorelin:
Sub cut or im 3-4 weekly. ( Gonapeptyl)
IM every 3 months ( Decapeptyl SR).
Side effects: Local, GI, asthenia, arthralgia .
Other products licensed in USA. Products under trial.

33. Behavioural interventions
Peer relationships in school/tall stature.
Adults raised expectations.
No evidence of long term psychological sequel.
Protection from inappropriate relationships
Patient education.
Play therapy & or psychology referral for child and family with significant issues.

34. References Hospital paediatrics: A.Milner/D.Hull
Nelson text book of pediatrics:18th Edition
BNF for children
Paediatrics. Clinical guide for nurse practitioners.
Essential paediatrics: David Hull